Peptide name : M1-20

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : D

Peptide length: 30

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : CCK-8 assay

Assay time : 36-h

Activity : IC50 = 23.57 µM

Cell line : ZR-75-30

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 3571.167 Dalton

Aliphatic index : 0

Instability index : 86.8633

Hydrophobicity (GRAVY) : -0.966

Isoelectric point : 11.717

Charge (pH 7) : 5.7604

Aromaticity : 3.333

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : infinite

hydrophobic moment : 0

Missing amino acid : A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y

Most occurring amino acid : r

Most occurring amino acid frequency : 6

Least occurring amino acid : q

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (30, 33., 30)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)O)[C@@H](C)O

1 : Bu H, et al. Development of an interfering peptide M1-20 with potent anti-cancer effects by targeting FOXM1. Cell Death Dis. 2023; 14:533. doi: 10.1038/s41419-023-06056-9

Paper title : Development of an interfering peptide M1-20 with potent anti-cancer effects by targeting FOXM1.

Doi : https://doi.org/10.1038/s41419-023-06056-9

Abstract : Disrupting protein-protein interactions (PPIs) has emerged as a promising strategy for cancer drug development. Interfering peptides disrupting PPIs can be rationally designed based on the structures of natural sequences mediating these interactions. Transcription factor FOXM1 overexpresses in multiple cancers and is considered an effective target for cancer therapeutic drug development. Using a rational design approach, we have generated a peptide library from the FOXM1 C-terminal sequence and screened FOXM1-binding peptides. Combining FOXM1 binding and cell inhibitory results, we have obtained a FOXM1-targeting interfering peptide M1-20 that is optimized from the natural parent peptide to the D-retro-inverso peptide. With improved stability characteristics, M1-20 inhibits proliferation and migration, and induces apoptosis of cancer cells. Mechanistically, M1-20 inhibits FOXM1 transcriptional activities by disrupting its interaction between the MuvB complex and the transcriptional co-activator CBP. These are consistent with the results that M1-20 suppresses cancer progression and metastasis without noticeable toxic and side effects in wild-type mice. These findings reveal that M1-20 has the potential to be developed as an anti-cancer drug candidate targeting FOXM1.